Title: Systematic review and meta-analysis of data relating to wheat bran intake and blood
lipids, specifically triglycerides.
Jolene McMonagle PhD1, , Reg J. Fletcher 1, Janice I. Harland PhD2
GL7 5HN England
2Kellogg European Headquarters
Airside Business Park,
GL7 5HN England
Author responsible for correspondence:
Short title/running head:
Effect of wheat bran fibre on blood triglycerides
wheat bran, blood lipids, triglycerides, cardiovascular risk
Text word count: 247
To review the evidence relating to wheat bran fibre intake (WBF) and their effect on blood
Systematic review and meta-analysis of intervention studies reporting WBF intake and blood
lipids, specifically triglycerides concentrations (TAG).
Medline and other scientific databases were searched for the period 1966–2011 to produce a
full reference list of articles for review.
A matrix of eligibility for study inclusion was established; 13 intervention studies conducted
with 281 broadly healthy adults met the criteria and were retained for further analysis. Using
standard meta-analysis techniques, standard mean difference in blood lipids following WBF
intake were calculated. Meta-regression analysis of added WBF intake on mean difference
blood TAG was also conducted.
Diets incorporating an average of 17.3 g/day WBF resulted in a reduced standard mean
difference in blood TAG of 0.178 mmol/L, (95% CI -0.303, -0.053), P=0.005. There was
some evidence of an inverse dose-response relationship between added wheat bran intake (g
dietary fibre /day) and net change in mean TAG, which failed to reach statistical significance,
There were minor changes and significant heterogeneity in other blood lipid data, except for
very low density lipoprotein (VLDL) cholesterol, which on the basis of limited data from
four studies was reduced by -0.102 mmol/L (95% CI -0.162, -0.043), P=0.001.
The addition of 17.3g /day WBF to the diet significantly lowered blood TAG by 0.178
mmol/L, equivalent to 8.6% reduction compared to baseline, without adverse effects on other
MetS and personalised nutrition
Elevated plasma TAG concentrations and low levels of high-density lipoprotein (HDL)
cholesterol are recognised cardiovascular risk factors, although attention is usually focussed
on low density lipoprotein (LDL) cholesterol as a prime risk factor. The pivotal role that
plasma TAG concentrations play in lipid metabolism is the subject of a recent consensus
statement from the American Heart Association (AHA), who after reviewing the evidence,
has confirmed that blood TAG, more appropriately, represent a biomarker of CHD risk rather
than an independent risk factor 1. However, it is recognised that in some individuals at risk
from cardiovascular disease (CVD) or insulin resistance (Ri), low density lipoprotein (LDL)
-cholesterol levels may not be elevated, but TAG levels are raised. In recognition of the
importance of TAG, the AHA scientific statement suggests the following new designations:
optimal fasting TAG levels are defined as <100 mg/dL (1.13 mmol/L), as a parameter of
metabolic health, borderline high fasting TAG levels are 150 to 199 mg/dL ( 1.7 to 2.2
mmol/L), high levels are 200 to 499 mg/dL ( 2.3 to 5.6 mmol/L) and very high levels ≥500
mg/dL (5.6 mmol/L). This reduction of the upper "normal" level of TAG to (≥ 1.7 mmol/L)
was also recently endorsed in a critical appraisal of the evidence relating to elevated levels of
triglyceride-rich lipoproteins (TRLs) by the European Atherosclerosis Society Consensus
Panel 2, who also recommended the targeting of elevated TAG (≥ 1.7 mmol/L) as a marker of
An extensive collaborative review of 101 studies identified that those with a genetic tendency
for high levels of triglycerides also had a greater risk of heart disease, providing evidence for
a causal association between triglyceride-mediated pathways and CHD 4.
Approximately 31% of the adult US population has a triglyceride level > 1.7mmol/L with no
appreciable change between the National Health and Nutrition Examination Surveys
(NHANES) of 1988–1994 and 1999–2008 data 1. Where increases in TAG have been
observed, this is primarily in younger age groups (20 to 49 years old), and overall, TAG
levels continue to be higher than in less industrialized societies 1. Taking a longer
perspective, mean TAG levels have risen since 1976, associated with exponential increases
in obesity, insulin resistance, and type 2 diabetes, while LDL cholesterol have not changed.
Quantification of the association between serum TAG and the risk of CHD was recently
undertaken using data from the European Prospective Investigation of Cancer (EPIC)-
Norfolk and Reykjavik studies 5. Two separate nested case-control comparisons were
conducted involving 3582 incident cases of fatal and nonfatal CHD and 6175 controls
selected from among the 44,237 men and women screened in the population studies. The
long-term stability of log-triglyceride values (within-person correlation coefficients of 0.64
(95% CI 0.60, 0.68) and 0.63 (95% CI 0.57, 0.70) over 4 and 12 years respectively) was
similar to those of blood pressure and total serum cholesterol. After adjustment the strength
of the association was attenuated, and the adjusted odds ratio (OR) for CHD was 1.76 (95%
CI 1.39, 2.21) in the Reykjavik study and 1.57 (95% CI 1.10, 2.24) in the EPIC-Norfolk
study, when the top third of individuals were compared with those in the bottom third of
values. A meta-analysis involving a total of 10,158 CHD cases from 262,525 participants in
29 studies also indicated an increased risk of CHD with elevated blood TAG; adjusted OR
was 1.72; (95% CI 1.56, 1.90) 5. Further epidemiological evidence is provided by a cohort of
1232 high-risk men aged 40-49 y followed for 23 years in the Oslo Diet and Antismoking
Trial. In this study normalising TAG, by lifestyle interventions in men with elevated TAG,
was associated with an reduced risk of ischemic heart disease (IHD) events; hazard ratio of
IHD events was 0.56 (95% CI 0.34, 0.93; P = 0.027) 6.
While an association between elevated TAG and CHD exists, the extent to which it is
independent of other risk factors of CHD remains less clear. For example, the treatment of
elevated TAG levels is often undertaken with interrelated lifestyle changes such as weight
loss; a 5% to 10% reduction in body weight may result in a triglyceride-lowering response of
20% with both factors contributing to the reduction in CHD risk 1. Elevated blood TAG is
also evident in Type 2 diabetics and high TAG levels accompanying either normal or
impaired fasting glucose can predict its development, as well as being one of the key risk
factors for the Metabolic Syndrome.Maintenance of normal blood concentration of TAG is
clearly a beneficial physiological effect and effective dietary management of elevated TAG
levels is an area that requires further attention. Contrary to traditionally-held opinion, it has
been shown that the long-term within-individual variability of TAG is no greater than that of
other lipid fractions 7; as such, it could provide a target for monitoring and intervention.
While an increase in fibre intake is considered desirable in diets for both diabetics and those
at risk from CHD, the focus of research has tended to be on the extent to which soluble
sources of fibre 8-11 or mixtures of whole-grain cereals can contribute 12. The objective of this
study was however, to investigate the role that can be played by well-characterised less
soluble cereal fibre, WBF, in modifying blood lipids specifically, blood TAG. In Western
populations, wheat is the predominant source of fibre or non-starch polysaccharide (NSP)
intake 13-15. Wheat bran has long been recognised as beneficial in gut transit and faecal
bulking16, although in studies related to blood lipid metabolism it has largely been considered
inert and has often been used as a control. A further objective of this study was to establish if
this assumption was valid.
Materials and methods
Computerised scientific publication databases were searched. The search was focused on
Medline (www.ncbi.nlm.nih.gov/entrez/query.fcgi) for the period January 1966 through to
November 2011 and was confined to human studies but no language restriction was imposed.
It was complemented by searches in EMBASE and hand search of key papers and references
cited in identified articles. In addition, the reference lists in identified papers were scrutinised
for further studies. Initial search terms were ‘wheat bran' or 'wheat fibre (fiber)' or 'cereal
bran or fibre (fiber)' or 'whole wheat' and 'blood or plasma or serum triglycerides' or
'cholesterol' or 'blood or plasma or serum lipids'. The search strategy was applied to titles and
abstracts only, in order to identify studies where interventions related WBF were the primary
intervention and not the control or placebo.
Data abstraction and quality assessment
The review of identified papers was conducted according to the QUORUM principles17 (Fig.
1). Studies were retained where the introduction of wheat bran fibre was a primary
intervention. Studies could be either crossover or parallel in design and should compare
WBF to baseline or a suitable control. WBF could be sourced from bran flakes or bran-rich
foods or whole wheat foods. Subjects were broadly healthy volunteers were healthy or mildly
hypercholesterolaemic, with average weight loss <1 kg/week and average BMI < 35; study
duration was a minimum of 3 weeks. Studies were excluded when participants were taking
lipid-lowering drugs or antihypertensive medication. The fibre content of the supplement
should be reported and measured using the method of the Association of Official Analytical
Chemists (AOAC), the Englyst method for non-starch polysaccharides (NSP), Southgate
method or a recognised method of dietary fibre analysis. Studies using a blend of different
cereal fibres or multiple cereals such as undefined wholegrains were excluded, as were
studies reporting fibre determined by crude fibre analysis.
Fig. 1 near here
The key characteristics of the studies were abstracted and the findings collated, which
included: identification of the number of subjects, gender, age, duration of study,
measurements of blood lipids, macronutrient content of the diet, definition of fibre and
method of assessment of intake. The data abstracted were subject to quality assessment in
three main areas: recruitment and flow of subjects through the study, dietary assessment and
treatment and reporting of data.
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software (Biostat, Englewood, NJ 07631, USA) was used for all statistical analysis
Fig. 1 outlines the results from the reported review process. The search identified 116 papers;
when abstracts were scanned and exclusion criteria applied, this resulted in 31 potentially
relevant studies. After reading the full articles, 14 treatment arms from 13 studies were
retained for further analysis 18-30. In addition to reporting some measure of blood lipids and
WBF intake, retained studies measured macronutrient intake. This could be reported as either
total intake, or the macronutrient content of the supplement where macronutrient content of
the background diet was kept constant. Studies were not retained for further analysis for the
following reasons: nutrient intake not matched or significantly different at baseline 31-34, no
nutrient intake data 35-37, primary objective not related to WBF or wheat bran treatment
inadequately characterised 38-42, subjects not healthy 43, inadequate study duration 22, 44 and
data values not presented or presented as figures unsuitable for further analysis or pooled data
presented 30, 45-46.
Details of the 13 retained papers that contained studies measuring blood lipids and with a
WBF intervention are shown in Table 1.
Table 1 near here
Retained studies included 8 randomised crossover studies (RX), 2 randomised controlled
parallel design (RCP) and 3 phased interventions, with and without WBF. Two studies were
single-blinded 19, 47, and one study double-blinded 24. Studies were conducted with 281 adult
male and females aged 18-73 years, most of whom were described as healthy, but included
mild hypercholesterolaemics and hypertensives. Study length ranged from 3-12 weeks, mean
4.6 weeks. The range of additional WBF intake was 10-22g /day. A number of analytical
techniques were used to measure fibre, most prevalent were AOAC and Southgate, which
can be expected to give similar results 48. Three studies measured NSP and by reference to
extensive data, these values were converted to be more similar to fibre determined by AOAC
by use of a conversion factor of 1.2, known to be appropriate for WBF. All studies apart from
two, reported macronutrient and energy intake 20, 26. The majority of studies were crossover
in design, the primary comparison made, was end of treatment values compared to control
end values. This approach was also used for the parallel studies, which were corrected for
baseline; for phased intervention studies end of intervention values were compared to
baseline. The average baseline blood TAG level was 1.52 mmol/L, with subjects from 2
treatment arms classified as borderline high 18, 27 and 2 classified as high 22.
Analysis of main outcomes
Thirteen treatment arms from 12 studies provided numerical data for the primary outcome,
blood TAG; when the data was pooled the inclusion of WBF in the diet resulted in a
significant standard mean difference in TAG of -0.178 mmol/L (95% CI -0.303, -0.053),
P=0.005. Heterogeneity was not evidence in the dataset, P =0.24. See Fig. 2. The inclusion of
an average of 17.3g WBF led to a mean reduction in TAG of 8.6% compared to baseline, but
when the mean reduction was calculated using the standard mean difference data, the
reduction compared to baseline was equivalent to 22%.
Figure 2 near here.
Figure 3 near here.
Meta regression was conducted to determine whether a dose-response relationship existed
between wheat fibre intake and net change in mean TAG. From Fig. 3, it can be seen that
there is some evidence of an inverse association between WBF intake (g dietary fibre/day)
and the reduction in TAG, however the relationship just failed to reach statistical significance,
Publication bias has been assessed by two methods, funnel plot of the standard error by
standard difference in mean TAG and Classic fail-safe N. The funnel plot is a plot of a
measure of study size (usually standard error) on the vertical axis as a function of effect size
on the horizontal axis, Fig. 4. Large studies appear toward the top of the graph, and tend to
cluster near the mean effect size. Smaller studies appear toward the bottom of the graph, and
(since there is more sampling variation in effect size estimates in the smaller studies) will be
dispersed across a range of values. In the absence of publication bias the studies are
distributed symmetrically about the combined effect size. This is broadly the case as shown in
Fig. 4. From this plot it can be seem that there is good symmetry around the centre line and
good distribution of the studies from top to bottom, there is a small indication of bias due to a
cluster of studies on the mid-left of the centre line. However when Classic fail-safe N is
calculated by incorporating data from 13 treatment arms, which yield a z-value of - 3.56 and
corresponding 2-tailed P-value of 0.0004. The fail-safe N is 30. This means that 30 'null'
studies would need to be located in order for the combined 2-tailed p-value to exceed 0.050
or there would be need to be 2.3 missing studies for every observed study for the effect to be
nullified indicating little evidence of bias.
Figure 4 near here.
When data relating to total, LDL- and HDL- cholesterol were pooled there was little effect on
these parameters with total cholesterol unchanged, a small reduction in LDL- cholesterol and
an increase in HDL- cholesterol. In all three datasets there was evidence of high degree of
heterogeneity (P<0.001) (data not shown).
Four studies 18, 20-21, 29, reported data related very low density lipoprotein (VLDL) cholesterol,
in all cases VLDL was reduced and when pooled, the simple mean difference was -0.102
mmol/L (95% CI -0.162, -0.043), P=0.001. Heterogeneity was not evident (P=0.058), but as
of borderline significance, a random effects analysis was also conducted, with little effect on
the outcome (-0.106 mmol/L, 95% CI -0.200, -0.011; P=0.029).
This is the first analysis that has specifically investigated the role of WBF intake on blood
TAG. The pooling of data from trials where there was an average intake of 17.2g dietary fibre
from wheat bran resulted in an overall significant effect on blood TAG of -0.178 mmol/L
(95% CI -0.303, -0.053) (Fig. 2) equivalent to a reduction compared to baseline of ca 9%.
From the meta regression it can be calculated that each 10g intake of dietary fibre intake was
associated with a reduction in TAG of approximately 0.1 mmol/L. The reduction in TAG was
associated with little effect on other blood lipids, with the exception of VLDL, where there
was also indication of a reduction in this lipid material. Previous assumptions that wheat bran
has little effect on blood cholesterol appear to be valid, although in respect of an effect on
blood TAG this clearly is open to question.
Nutrition modifications that can effect TAG levels have focussed on reducing overall energy
(e) intake, as it is recognised that weight loss has a beneficial effect on blood TAG 49.
Furthermore the magnitude of decrease in TAG is directly related to the amount of weight
loss and, by means of a meta-analysis, it has been estimated that for each kilogram of weight
loss, a decrease in TAG of 1.9% results 50,51. In this analysis, studies were selected where
weight loss was minimal and using the relationship described above by Anderson et al. 51, it
can be calculated that to account for the reported 8.6% reduction in TAG, there would have
had to have been a 4.5kg loss in weight, which was not the case.
Other aspects of nutrient intake that can influence TAG levels are total fat and available
carbohydrate intake 52. In a meta-analysis of 60 studies, a 1 % isoenergetic replacement of
saturated, monounsaturated or polyunsaturated fat with carbohydrate resulted in significant
increases in fasting TAG levels of 0.021, 0.019 and 0.026 mmol/L respectively, all P<0.001,
indicating a benefit from replacing available carbohydrate with fat. A similar effect was
reported when moderate fat diets (32.5% to 50%e from fat) were compared to lower-fat diets
(18% to 30%e from fat) with a resulting decrease in TAG of 0.1 mmol/L (range from -0.07
to - 0.14 mmol/L, P<0.00001) with the moderate fat diet 53. In subjects with diabetes the
moderate fat diet intervention led to an even greater reduction in TAG 53.
Within this database of studies macronutrient content of baseline and intervention was
matched to varying degrees. There was no significant differences in the macronutrient
content reported for retained studies, however there was a difference in fat intake between
baseline and the wheat and barley interventions of 20 and 19g respectively in one study 25 and
the supplement used in one study increased protein intake by ca 60g and reduced available
carbohydrate intake by ca 70g 22. Exclusion of these three treatments from the analysis
resulted in a reduction in mean TAG which was similar to the dataset as a whole (-0.166
mmol/L; 95% CI -0.312, -0.021; P=0.025). It therefore appears likely that the fibre or some
component of the bran is the causal agent for the reduction that we have reported.
The role of fibre intervention on blood TAG is less well documented particularly in non-
diabetic subjects, although fixed-effect meta-analyses techniques have been used to obtain
mean estimates of changes in blood lipids following dietary intervention in diabetics 54. High
carbohydrate, high fibre diets compared to moderate carbohydrate, low fibre diets were
associated with lower values for fasting, postprandial and average plasma glucose, total, LDL
and HDL-cholesterol and TAG. Overall indications were that high intakes of dietary fibre
(≥20 grams/1000 kcal) in the context of moderate or high carbohydrate diets led to improved
serum lipoproteins, with reported reductions in TAG of 8.3-12.8% 54. In this analysis, total
dietary fibre intake / 1000 kcal could be estimated in ten treatments 18-25, 47 and ranged from 8
- 24g/ 1000 kcal, while added dietary fibre from wheat bran was on average 17.3g (range 7-
36g ). From this analysis it can be seen that the addition of 17.3g dietary fibre from wheat
bran was associated with a reduction in TAG of 8.6%, not dissimilar to that reported for
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Wheat bran also is a source of minerals, vitamins and phenolic compounds. These phenolic
compounds provide the plant's defence system and include derivatives of benzoic and
cinnamic acid, the most extensively studied of which is ferulic acid 14. There is evidence that
intestinal microbes can release ferulic acid and other phenolics from the bran, hence these
substances or their metabolites are bioavailable and may be physiologically active, although
the mechanisms involved require further investigation 14. It is suggested that the
cardiovascular benefits may be related to folate, magnesium, vitamin B-6, vitamin E or serum
levels of enterlactone rather than the fibre per se 57.
In a recent analysis of the Nurses' Health Study, 7822 women with type 2 diabetes were
assessed for the risks of all cause and CVD mortality. After adjustment for age, lifestyle and
dietary risk factors, the strongest association that remained was an inverse association
between cereal bran intake and CVD-specific mortality. The relative risk across fifths of bran
intake were 1.0, 0.95, 0.80, 0.76 and 0.65 respectively ( P for trend = 0.04) 58. The
relationship was evident after adjustment, whereas no significant associations were evident
after adjustment, for whole-grain intake, for cereal fibre or germ intake. While cereal bran
will include other sources cereal fibre, it should be recalled that in both US and UK
populations wheat is the predominant source of whole grain cereals in the diet and is likely to
comprise at least half of cereal bran 14-15. A beneficial association between CHD and whole
grains intake in the US Health Professionals Survey also identified that the bran component
could be a key factor in the relationship 59. The mechanism responsible for this association
between cereal bran and CVD has not been identified and it conceivable reduction in blood
TAG may be a contributing factor.
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There are a number of limitations in this analysis, the quality of identified studies was
variable, few studies were blinded, the nature of the control was variable and a number of the
studies compared wheat with oats, where wheat bran it could perhaps be implied, was a
control treatment. The analytical determination of dietary fibre was undertaken principally by
AOAC technique, but NSP (adjusted) and other measures were also used giving rise to
another source of variation. The presentation of WBF to subjects took a variety of different
forms including bran supplements breakfast cereals, bread, biscuits, muffins, wheat whole-
grain foods and supplements. The effect which food processing techniques employed during
the manufacture of the WBF foods have on bioavailailabilty of WBF components critical for
the mechanism of action is uncertain.
Nevertheless the inclusion of a modest intake of wheat bran resulted in a small TAG lowering
effect, which may contribute to reduction of cardiovascular risk. Overall, its addition to
optimisation of nutrition interventions, such as reductions in available carbohydrate,
restriction in added sugars and fructose, reduction in trans and saturated fatty acid intake and
optimal consumption of long-chain omega-3 fatty acids can contribute to a TAG-lowering
effect that ranges between 20% and 50% 1.
The provision of a unconditional grant from the Kellogg Group of European Companies is
Table 1 Details of the intervention studies included in the present systematic review and analysis
41% e fat, 16%
e protein, 43% e
CHO 18g DF all
& eaten in
Control diet +
either wheat or oat
40g wheat bran
cereal + wheat bran
21days RCT P 20 M Hypocholesterolae
mic >5.2 mmol/L
TC, TAG <3.4
>28.7; 38-73 y, no
medication, but 14
had diagnoses of
Phase II AHA
diet to stabilise
Bread with oat bran
AACC 4wk RT SB
TC 5.7-9 mmol/L ,
Control diet all
& eaten in
+20g wheat bran
prepared as bread
7 wk PIT 4 M Healthy
Refined wheat Whole wheat
+13.3g F ex whole
AOAC 3wk RCT
54.5 y +/-7.6
Control diet all
& eaten in
Wheat bran +36g
3wk RT X 6 M Healthy
medium or ultra
Wheat bran and
gluten in prepared
AOAC 1mo RCT
Healthy (1 F on
HRT) BMI 17.9-
Kestin White bread Bread with 12g +12g/ NSP 4wk RCT 24M Mild
1990 24 Low fibre diet
wheat bran day
No control 2
wheat or barley
NSP 4wk RT X 21M Mild
6wk PIT 3 M/
Healthy 18-22 y
No control 2
AOAC 4 wk RT X 13M/
Free living obese,
BMI >29 to
< 40 kg/m2 with
glucose >6·1 and
≤ 7·1 mmol/L
3 servs whole-grain
NSP 12wk RCT
en 1979 29
Habitual diet Coarse wheat bran
to 37.8g wheat
4wk PIT 7 M Healthy, 18-24 y
No control, 3
breakfast cereals or
14g DF/ 4184 kJ
from All Bran/Bran
Buds + viscous
AOAC? 21 d RT X 12 M/
35 (SD 12) y
Abbreviations: NG - not given, M male, F female, wk week, RCT - randomised controlled
trial; P - Parallel; X - crossover study; PIT - Prospective intervention trial; DB - Double blind;
SB - Single blinded; F fibre; DF dietary fibre; NSP non starch polysaccharides; BWt body
weight; servs servings; C= control; I = intervention;
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